The long term objectives of this program continue to be directed toward; a) the investigation and delineation of the sensitivity and time and dose dependent responses of proliferating endothelial cells in vessels induced by the angiogenesis factor(s) from tumor tissue, following exposure to ionizing radiation, hyperthermia or selected therapeutic chemicals, b) investigation of the consequences of these responses on the integrity of the tumor vasculature in terms of changes in vessel blood flow, caliber, numbers an ddistribution and, c) development of a base of knowledge, concerning endothelial and vascular responses to therapeutic agents, which is essential not only for investigations directed toward therapeutically optimal combinations of these agents but also for better understanding of vascular mechanism involved in the responses of tumor parenchyma to therapeutic treatment. To progressd toward these objectives, the following specific aims are both in progress and are planned; a) autoradiographic determination of the temporal changes in endothelial cell proliferation in relation to responses in tumor parenchyma following irradiation, hyperthermia or selected drugs (adriamycin and ICRF-159), b) quantitative histologic determination of the temporal changes in morphometric relationships between vascular, parenchymal and stromal components within the tumor following these treatments and, c) video/electronic determination of the temporal changes in erythrocyte velocity, blood flow and vessel caliber in tumor and normal vasculature in response to these treatments. For these studies the cervical carcinoma is being grown in the transparent cheek pouch chamber of the Syrian hamster. The use of this system provides a clear visualization of the tumor vascular network required for RBC velocity and diameter measurements and provides a unique opportunity for correlating in vivo pathophysiologic changes in the vessels with quantitative histologic and autoradiographic data.